rs372789789

Variant names:

• chr10-86699302-C-T
• rs372789789
• NM_001368067.1:c.780C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-86699302-C-T
• chr10-86699302-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS1

The NM_001368067.1(LDB3):​c.780C>T​(p.Asn260Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.000344 in 1,613,612 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: LDB3 NM_001368067.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 4.50
• Publications: 1 publications found

Genes affected

LDB3 (HGNC:15710): (LIM domain binding 3) This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]

LDB3 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: ClinGen
• myofibrillar myopathy 4

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 10-86699302-C-T is Benign according to our data. Variant chr10-86699302-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000579 (88/151898) while in subpopulation AMR AF = 0.00164 (25/15260). AF 95% confidence interval is 0.00114. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368067.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	NM_001368067.1	MANE Plus Clinical	c.780C>T	p.Asn260Asn	synonymous	Exon 9 of 9	NP_001354996.1	A0A0S2Z530
	LDB3	NM_007078.3	MANE Select	c.896+6731C>T		intron	N/A	NP_009009.1	O75112-1
	LDB3	NM_001171611.2		c.1125C>T	p.Asn375Asn	synonymous	Exon 9 of 9	NP_001165082.1	O75112-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.780C>T	p.Asn260Asn	synonymous	Exon 9 of 9	ENSP00000263066.7	O75112-6
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2430C>T	p.Asn810Asn	synonymous	Exon 18 of 18	ENSP00000393132.2	C9JWU6
	LDB3	ENST00000372056.8	TSL:1	c.1125C>T	p.Asn375Asn	synonymous	Exon 8 of 8	ENSP00000361126.4	O75112-4

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 151898 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000498 AC: 124 AN: 249002 AF XY: 0.000422

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000665

Gnomad OTH exome AF: 0.000660

GnomAD4 exome AF: 0.000319 AC: 467 AN: 1461714 Hom.: 1 Cov.: 35 AF XY: 0.000347 AC XY: 252 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000326 AC: 363 AN: 1111976

Other (OTH) AF: 0.000265 AC: 16 AN: 60386

GnomAD4 genome AF: 0.000579 AC: 88 AN: 151898 Hom.: 0 Cov.: 32 AF XY: 0.000674 AC XY: 50 AN XY: 74150

African (AFR) AF: 0.00 AC: 0 AN: 41320

American (AMR) AF: 0.00164 AC: 25 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.000567 AC: 6 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000824 AC: 56 AN: 67988

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.000625 Hom.: 0

Bravo AF: 0.000416

EpiCase AF: 0.000491

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated cardiomyopathy 1C;C4721886:Myofibrillar myopathy 4 (1)
-	-	1	Myofibrillar myopathy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Benign	0.72
PhyloP100		4.5
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs372789789; hg19: chr10-88459059;